Cloning and characterization of the mouse vitamin D receptor promoter
Cloning and characterization of the mouse vitamin D receptor promoter
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DOI：
10.1073/pnas.94.19.10138
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发表时间：
1997-09-16
影响因子：
11.1
通讯作者：
DeLuca, HF
中科院分区：
文献类型：
--
作者：
Jehan, F;DeLuca, HF
编码小鼠维生素D受体的基因已被克隆。已经发现了一个新的外显子1，其改变了为人类VDR基因建立的编号，人类VDR基因中的外显子2和3（分别编码锌指1和2）在小鼠维生素D受体中被命名为外显子3和4。分析了新外显子1的1.5 kb 5 '侧翼区，发现存在推定的顺式作用元件。尽管缺少TATA盒，但该5 '侧翼区含有富含GC的启动子的几个特征，包括串联存在的四个Sp1位点和两个CCAAT盒。有趣的是，最接近新外显子1的Sp1位点与Krox-20/24的完美位点重叠。Krox-20是一种参与脑发育和骨重塑的转录因子，在荧光素酶报告基因表达测定中，我们表明来自该5 '侧翼区的序列引起高的反式激活活性。此外，在NIH 3 T3细胞系中，观察到对毛喉素处理（腺苷酸环化酶的激活剂，进而是蛋白激酶A途径的激活剂）的响应增加3- 5倍。
The gene encoding the mouse vitamin D receptor has been cloned. A new exon 1 has been found that changes the numbering established for the human VDR gene, Exons 2 and 3 in the human VDR gene (coding for the zinc fingers 1 and 2, respectively) are named exons 3 and 4 in the mouse vitamin D receptor. The 1.5-kb 5'-flanking region of the new exon 1 was analyzed and revealed the presence of putative cis-acting elements. Despite the absence of a TATA box, this 5'-flanking region contains several characteristics of a GC-rich promoter including four Sp1 sites present in tandem and two CCAAT boxes. Interestingly, the Sp1 site that is the most proximal to the new exon 1 overlaps a perfect site for Krox-20/24. Krox-20 is a transcription factor involved in brain development, and also in bone remodeling, In luciferase reporter gene expression assays, we showed that sequences from this 5'-flanking region elicit high transactivation activity, Furthermore, in the NIH 3T3 cell line, a 3- to 5-fold increase in response to forskolin treatment (an activator of adenylate cyclase and in turn of protein kinase A pathway) was observed.